A. The atrial natriuretic factor A receptor mRNA has been detected on small cell lung cancer cells by PCR analysis of cDNA from the cell lines and RNase protection assay. Binding studies with iodinated ANF showed saturable binding but the number of sites on the small cell lung cancer cell lines, NCI-H82, NCI-H660, NCI-H1284, were to low to accurately estimate. The cells respond to exogenously added atrial natriuretic factor with an increase in intracellular cGMP, similar to the normal receptors. Therefore, there appear to be functional ANF receptors on the surface of small cell lung cancer cells. B. The serum and urine calcitonin values of 86 different individuals were studied by radioimmunoassay which included 20 nonsmokers, 17 smokers, and 49 patients with small cell lung cancer. The urine values were the most different in these three groups of individuals (p is less than or equal to 0.00001). RNase protection assays (RPA) and RIAs of 16 tumor cell lines from these patients with small cell lung cancer showed five had elevated serum and/or urine calcitonin values but did not have ectopic calcitonin production in their tumor cell lines. Therefore, it appears that elevated calcitonin levels in patients with lung cancer can come from a source other than the tumor cells.